Preparation of fluoroalcohols by reaction of fluoroketones with selected hydrogen donors



United States Patent OfiTice 3,350,742 Patented Dec. 5, 1967 PREPARATION OF FLUGROALCOHOLS BY REAC- TION F FLUOROKETONES WITH SELECTED HYDROGEN DONORS Thomas A. Ford, Hockessin, Del., assignor to E. I. du Pout de Nemours and Company, Wilmington, Del., a corporation of Delaware No Drawing. Filed Mar. 2, 1965, Ser. No. 436,632

11 Claims. (Ci. 260617) ABSTRACT 0F THE DISCLGSURE Preparation of selected fluoroalcohols by reduction of haloketones with aldehydes, alcohols or formates at elevated temperature and optionally in the presence of a basic catalyst, and also the single novel alcohol lH-hexafiuorocyclobutanol useful as a solvent.

This invention relates to, and has as its principal object provision of, a novel process for the synthesis of selected fiuorinated alcohols. Provision of a novel fluoroalcohol, lH-hexafluorocyclobutanol, is another object of the invention.

It is known to prepare secondary fiuoroalcohols by reduction of the corresponding fiuoroketones either by treatment with complex metal hydrides such as lithium aluminum hydride or sodium borohydride, or by catalytic hydrogenation under pressure in the presence of platinum or copper/ chromium oxide catalysts. These prior methods are not free from disadvantages. Thus, the first one involves the use of highly inflammable and expensive reducing agents in organic solvent systems. In the second one, the impurities which are normally present in the fluoroketones tend to poison the catalyst unless the fluoroketone is specially and carefully purified beforehand.

The present invention avoids such disadvantages as are enumerated above by means of a process for preparing fluorinated secondary alcohols in which (1) certain polyhaloketones are reacted with (2) certain hydrogen donors by contacting the same at a temperature of at least 100 C. In the absence of a reaction catalyst, the reaction must be carried out at a temperature of at least 150 C., and preferably at least 200 C.

The formula of the polyhaloketone reactant may be written as R COR where R and R alike or different, are perfiuoroalkyl, w-hydroperfiuoroalkyl, w-chloroperfluoroalkyl or w-dichloroperfluoroalkyl of up to 8 carbons. R and R can also constitute a single divalent radical of the formula CF CF C(X X where X and X alike or different, are fluorine or chlorine. The resulting alcohols have the formula Suitable hydrogen donors are those of the formulae R CHO, R CHOHR and HCOOR where R and R alike or different, are hydrogen or alkyl of up to 6 carbons. Specific usable hydrogen donors include: lower aliphatic aldehydes, e.g., formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, n-hexanal, etc.; lower primary and secondary alkanols, e.g., methanol, ethanol, l-propanol, 2-propanol, isobutyl alcohol, see-butyl alcohol, l-pentanol, Z-pentanol, l-hexanol, 3-hexanol, etc.; formic acid, HCOOH; and lower alkyl esters of formic acid, e.g., methyl, ethyl, propyl, butyl or n-hexyl formate, etc.

Suitable catalysts are bases of the group consisting of alkali or alkaline earth metal hydroxides, alkali metal salts of acids with a dissociation constant lower than 2X10, and tertiary amines. Specific usable catalysts include: alkali metal hydroxides, e.g., LiOH, NaOH, KOH, RbOH, and CsOH; alkaline earth metal hydroxides, e.g., Be(OH) Mg(OH) Ca(OH) Sr(OH) and Ba(OH) alkali metal salts of formic acid or weaker acids, e.g., the formates, acetates, propionates, lactates, phenolates, carbonates, bicarbonates, borates, and silicates of Li, Na, K, Rb, and Cs; and tertiary amines, e.g., pyridine, N-methylpiperidine, trimethylamine, triethylamine, tributylamine, tri(cyclohexyl)amine, N,N-dimethylaniline, etc.

Reaction in the absence of a catalyst requires a temperature above 150 C. and preferably in the range 200-300 C. in order to obtain a useful extent of reaction in a reasonable time. At 250-300 C., nearly quantitative conversions are obtained in 16 hours or less. There is no advantage in exceeding a temperature of about 400 C. With a catalyst of the type mentioned above, the reaction occurs slowly at 50 C., but is preferably run at above C., and especially conveniently at 300 C. where reaction is rapid and substantially complete in 16 hours or less.

It is desired that the reaction mixture be confined in a pressure vessel, where the pressure is conveniently 50 to 1000 atm., as determined by the autogenous pressure of the reactants, but may be lower than 50 atmospheres (with correspondingly lower diminished space-time yield) or higher than 1000 atmospheres (by application of compression).

Diluents may be added, especially if needed to solubilize the catalyst, but are generally unnecessary. The organic hydrogen donor generally serves as a reaction medium in which the catalyst has adequate solubility. The quantity of catalyst required is small. It can be as low as 1 mole percent and seldom needs to be more than 10 mole percent based on the fluoroketone to be reduced. The relative proportions of the hydrogen donor and fluoroketone are not critical since the reaction will proceed regardless of what they are. Generally, the hydrogen donor is used in a molar ratio with respect to the fluoroketone of at least 0311 and preferably at least 0.75: 1. A slight to moderate molar excess of the hydrogen donor, e.g., 1.02:1 to 12:1, generally gives best results in that it is usually the less expensive reactant, and also because an excess of unreacted hydrogen donor is easier to separate from the product fiuoroalcohol than is unreacted fluoroketone remaining when the fluoroketone is used in excess. There is generally no advantage in exceeding a molar ratio of 1.5 :1.

The reaction product can be isolated by conventional fractionation procedures. In some cases, however, some or most of the secondary fluoroalcohol is obtained as a constant boiling mixture containing minor amounts of the hydrogen donor 'and/or by-products of the reaction. If desired, these azeotropes can be subjected to a separating operation, for example a chromatographic treatment, to obtain the fiuoroalcohol in a pure state. Such an operation is, however, generally unnecessary for most of the uses to which the fiuoroalcohols are put. Formic acid shows no tendency toform such azetotropes, and it is therefore the preferred hydrogen donor, as its use affords clean-cut reactions and excellent yields.

EMBODIMENTS OF THE INVENTION There follow some nonlimiting examples illustrative of the invention in more detail. In these examples, pressures are autogenous unless otherwise indicated. In Examples 1 and 2, the carbon monoxide introduced into the reaction mixture was intended to induce a reaction different from that observed. The expected reaction did not take place, so that the carbon monoxide acted solely as in inert pressuring agent.

Example I A 240 rnL-capacity pressure vessel lined with Hastel- 4 Example 3 A 400-ml. silver-lined pressure vessel was charged with 27.6 g. (0.6 mole) of formic acid and 5.1 g. (0.075 mole) of sodium formate. The vessel was closed, cooled and 5 partially evacuated, and 125 g. (0.75 mole) of hexa- 3 C cofnmerclal nlckel-lron-molybenuin alloy) fluoroacetone was added. The valve was closed, and the was charged with m of formlc acld- It was vessel was shaken and heated. The reaction mixture was then Closed, Cooled, and Partlany evacuated: and 83 maintained at 250 C. for 16 hours at autogenous pres- 111018) hexafluqroacewne was q f The Vessel sure. The vessel was cooled to 0 C., gases were vented, was installed in a barricaded shaker macmne, pressured 10 and the liquid product was discharged It was filt d to while cold wlth carbon monoxide to 200 atm., and heated remove a white solid, 33 g and the clear liquid was then with shaking. The temperature was held at 120 C. (dedistilled. veloped pressure, 400 atm.) for 2 hours, then at 150 C. The main fraction, 786 g C. 245 for 1 34 at (490 mm) for 4 1.2775, was 2I-I-hexafluoro-2-propanol, with a small hours- Thare was 9 slemficant P drop at any of 15 amount of an impurity indicated by a minor absorption these temperatures, indicatlng that the carbon monoxide peak at in the infrared Spectrum which was otherwas not involved in the reaction. The reaction vessel was wise that of pure 2H h fl 2 1 then cooled, the gases were vented off, and the remaining Examples liquid product was distilled. The low-boiling (53-99 C.) 1 fraction comprising about 25% of the liquid product E A forth In Table be w Show showed strong infrared absorption bands characteristic actlqns w same manner as m Example 3, with the variations indicated in the table. Example 4 of 2H hexafiuoro 2 propanol.

shows the use of pyridine in place of sodium formate Example 2 as catalyst. Examples 5 to 9 show that the optimum results with a basic catalyst are obtained at temperatures A Hastenoy C-hned Pressure Vessfil Was above 100 C., while Examples 10 and 11 show that charged Wlth gmole) of methanol and 83 Without a basic catalyst the yields are lower at equivalent (0.5 mole) of hexafiuoroacetone, and heated under prestemperatures, and that a temperature of about 200 C. sure of Carbon monoxide at for or higher is necessary to obtain practical results. 8 hours. It was then cooled to 0 C., the gases were vented Th experiments employing f r i i in molar 01f, and the liquid product, 69 g., was discharged and cess over the hexaflu'oroacetone gave, upon simple fracfract onally distilled at atmospheric pr s e. tional distillation, pure 2H-hexafluoro-2-propanol, as There Was Obtalned a fractlon, shown by the infrared spectra and refractive indices, withwhich was essentially p H-h -2-p out any of the minor impurity noted in Example 3 and Panol as Shown y Its boillng P refractive indeX 3 other experiments in which hexafluoroacetone was used ("13 NMR Spectrum, and infrared Spectrum; 5 in excess. This high purity was confirmed by gas chroall intermediate fraction of matography in the case of Example 5, in which the fore- "13 an a fraction, shot, B.P. 56-57 0., 1.2780, 25 g., and the two "13 a. HR "D main fractions, B.P. 57-58 0., n 12780-12782, and (e) 1.1 g. higher boiling. An additional 2.8 g. of 234 g., were analyzed, and all were indicated to be 99% product, n 1.2730, was recovered from a cold trap pure.

TABLE I Example Vessel HCOOH, HFA, Catalyst, Temp., Weight Yield HFIP,

Moles Moles Moles C. HFIP, g. Percent .8 .75 .075, pyridine--- 250 102 81 (on HFA). 2.0 1.9 0.1, HCOONa 250 204 83 (onHFA). 2.0 1.9 0.1, HCOONa 200 273 85 (on HFA). 2.0 1.9 0.1, HCOONa 150 282 88 (onHFA). 2.0 1.9 0.1, HCOONa 100 186 as (on HFA).

.6 .75 .075, HCOONa -4 -4 (on HCOOH). .6 .75 250 65.7 65 (0111300011). .6 .75 150 Trace 1.

1 Vessel A was of 400 ml. capacity, silver lined. I Vessel B was of 1,200 ml. capacity, Haste110y" C lined. ,HFA is hexafluoroacetone. HFIP is 2H-hexafiuoro-2-pr0pano1.

connected to the still during distillation, by allowing the Example 12 trap to warm slowly to room temperature while the lowboiling material (excess hexafiuoroacetone) boiled oil.

In this preparation, some methyl formate was obtained as a coproduct. The fraction (c) with B'.P.- 72-73 C. was found by NMR and infrared spectra to be a mixture (azeotropic) of 2H-hexafluoro-2-propanol with methyl formate, having a (CF CHOH/HCOOCH mole ratio of 2/ 1, or weight ratio of 85/15. The total weight of 2H-hexafluoro-2-propanol recovered in the various fractions was estimated to be about 34 g., or 0.2 mole, from 0.2 mole of methanol.

Methyl formate and ZH-hexafiuoro-Z-propanol were also formed when hexafluoroacetone was heated with methanol and sodium methoxide to 250 C. under autogenous pressure.

A 400-ml. silver-lined pressure vessel was charged with 48 g. (0.8 mole) of methyl formate, 5.1 g. (0.075 mole) of sodium formate, and g. (0.75 mole) of hexafluoroacetone. The mixture was agitated and heated for 16 hours at 250 C. After the vessel was cooled and vented, the liquid product was discharged, filtered, and distilled at atmospheric pressure. The major product, BR 67- 72 C., n 1.2922, amounted to 49' g., and was shown by its infrared spectrum to be a mixture of the azeotropc of methyl formate and 2H-hexa-fiuoro-2-propanol with minor amounts of impurities.

Example 13 A 400-ml. silver-lined pressure vessel was charged with 48 g. of 37% formaldehyde solution containing approximately 17.8 g. (0.6 mole) of CH O, 6.0 g. (0.2 mole) of CH OH, and 24.2 g. (1.3 mole) of water. The vessel was closed, cooled, and partially evacuated, and 125 g. (0.75 mole) of hexafiuoroacetone was added. The mixture was agitated and heated at 250 C. under autogenous pressure for 16 hours. It was then cooled and Vented, and the liquid product was discharged and distilled at atmospheric pressure.

A 17-g. fraction, B.P. 58 C., n 1.2770, having the infrared spectrum of pure 2H-hexafluoro-2-propanol was the first product distilled over. Subsequent fractions included: 19 g. of a mixture with a constant boiling point of 67.5 C., mostly 2H-hexafiuoro-2-propanol and methyl formate (mole ratio 9:1 by NMR), the latter being formed because of a side reaction; 54.5 g. of another mixture with a constant boiling point of 80 C., mostly 2H-hexafluoro-2-propanol with small percentages of methanol and water; and 38.6 g. of additional fractions having intermediate boiling point ranges.

Example I 4 A 400-ml. silver-lined pressure vessel was charged with 48 g. (0.8 mole) of isopropyl alcohol and 125 g. (0.75 mole) of hexafiuoroacetone, and the mixture was agitated and heated for 16 hours under autogenous pressure at 250 C. The vessel was cooled to 0 C., vented, and the liquid product Was discharged and distilled. Fractions having boiling points of 84 C. (11.9 g.) and 9l.593 C. (120.7 g.) were obtained, along with some foreshot and 8 g. of an intermediate fraction. NMR and infrared spectra indicated the first of these azeotropes to be 2H-hexafluoro-Z-propanol (ca. 77% by weight) with acetone, water, and isopropyl alcohol, and the second to be 2H- hexafiuoro-Z-propanol (ca. 75% by Weight) with acetone and isopropyl alcohol. The indicated conversion of hexafiuoroacetone to ZH-hexafluoro-Z-propanol was about 85%.

Example 15 A 400-ml. silver-lined pressure vessel was charged with 36.8 g. (0.8 mole) of formic acid, 5.1 g. (0.075 mole) of sodium formate, and 149.2 g. (0.75 mole) of 1,3-di- 5 chloro-1,1,3,3-tetrafluoroacetone. It was then closed and the mixture was agitated and heated under autogenous pressure at 250 C. for 16 hours. The vessel Was then cooled to 0 C., vented, and the liquid product was discharged, filtered to remove a small amount of solid (2.2 g.) and distilled. After 15 g. of foreshot, 71 1.3686, there was recovered 101 g. of 1,3-dichloro-1,1,3,3-tetrafiuoro-2- propanol, B.P. 108110 C., n 13706-13710, corresponding to a conversion of 68% of the starting ketone to the corresponding secondary alcohol.

Example 16 An 80-ml. Hastell'oy-lined pressure vessel was charged with 5.1 g. (0.111 mole) of formic acid, 0.75 g. (0.011 mole) of sodium formate and 21.5 g. (0.12 mole) of hexafluorocyclobutanone, and the mixture was agitated and heated for 15 hours at 250 C. under autogenous pressure. The vessel was then cooled to 0 C., the gases were vented off, and the liquid product was discharged. Distillation in the presence of a small amount of added sodium fluoride yielded 9.5 g. of fractions boiling at 66- 69 C. and 2.2 g. of higher-boiling liquid. A representative fraction boiling at 69 C. was shown by elemental and spectral analyses to be 1H-hexafluorocyclobutanol,

AnalySis.CalCd. for O l-1 1 0: C, 26.68; H, 1.12; F, 63.31. Found: C, 27.23; H, 1.31; F, 62.94.

The infrared spectrum showed absorption peaks at 298 (OH), 3.37 1 (saturated 0-H), and strong absorptions in the 7.5-10,u region for CF and/or CO. The nuclear magnetic resonance spectrum also confirmed the structure.

1H-hexafluorocyclobutanol is a new compound. It has good solvent power for various polymeric materials, as exemplified by the fact that it readily dissolves commercial polymethyl methacrylate and polyhexamethyleneadipamide.

The process of this invention is applicable to any polyfiuoroketone having the general formula previously set forth. Other specific examples of operable fluoroketones Pei-fluoro-(2,4-dimethyl-3-pentanone) (CFa)2CFCO CF(CF 1,1,3-trichloro-L3,3-trifiuoropr0panone OFChCO OFzCl 1,1,3,3-tetrachl0ro-1,3-difiuoropropan0ne CFClzOOCFCh 1,1,3,3-tetrafluoropropanone HO F20 O C FzH 3H-per1lu0r0-(2,4-dimethyl-3-pentan01) (CFmOFCHOHCMOFm 1,1,3-trichloro-1,3,3-trifiuoro-2-propanel CFClzCHOHCFzCl 1,1,3,3-tetrachloro-1,3-diflu0ro-2-propanol CFC12CHOHCFC12 TABLE IIContinued Ketone Product pcntanol are listed in Table II, together with the fiuoroalcohols resulting from reaction with any of the hydrogen donors enumerated above.

The fluoroalcohols obtained in this process are widely useful as solvents, plasticizers, dispersing media, and reactlon media. It is disclosed in US. Patent 3,129,053, for example, that secondary fiuoroalcohols of the type obtainable by the present process, e.g., ZH-hexafiuoro-Z-propanol, 1,3 -dichloro-1,1,3, 3 -tetrafiuor-2-propanol, and many others, are excellent dispersants for normally insoluble or very poorly soluble organic pigments. Furthermore, by virtue of their low surface tension and extraordinary solvent ability, associated with their high hydrogen-bonding power, they are able to penetrate deeply into practically all substrates, even those of low porosity. Still furthermore, fiuoroalcohols of this type have unusual solvent power for high molecular Weight, synthetic, linear condensation polymers, for example, formaldehyde polymers, nylons, polyimides, polycarbamides, polycarbonates, polycarbarnates, and hydrolyzed polyvinyl esters. With such polymers, for which very few low-temperature solvents are known, secondary fiuoroalcohols of the type described form homogeneous, stable solutions even at room temperature. There solutions can be used to form shaped articles such as films or filaments from the polymers, or in other applications such as adhesive compositions.

Since obvious modifications and equivalents in the invention will be evident to those skilled in the chemical arts, I propose to be bound solely by the appended claims.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. The process of producing a secondary fluoroalcohol which comprises reacting, at a temperature between 100 and 400 C. and at at least autogenous pressure, a polyfiuoroketone of the formula wherein R and R are selected from the group consisting of perfiuoroalkyl, w-hydroperfluoroalkyl, w-chloroperfiuoroalkyl and w-dichloroperfiuoroalkyl of up to 8 carbons and CF CF C(X X X and X being selected from the group consisting of fluorine and chlorine, with a hydrogen donor selected from the group consisting of R CHO, R CHOHR and HCOOR, R and R being selected from the group consisting of hydrogen and alkyl of up to 6 carbons.

2. The process of claim 1 employing a basic catalyst selected from the group consisting of alkali and alkaline earth metal hydroxides, alkali metal salts of acids having dissociation constants lower than 2 l0- and triethyl-, trimethyl-, tributyland tri(cyclohexyl)amine, pyridine, N-methylpiperidine and N,N-dimethylaniline,

3. The process of claim 1 employing a slight to moderate excess of the hydrogen donor over the polyfiuoroketone.

4. The process of claim 1 wherein the polyfluoroketone is hexafiuoroacetone.

5. The process of claim 1 wherein the polyfluoroketone is 1,3-dichl0ro-1,1,3,3-tetrafiuoroacetone.

6. The process of claim 1 wherein the polyfiuoroketone is hexafiuorocyclobutanone.

7. The process of producing ZH-hexafiuorO-Z-propanol according to claim 1 which comprises reacting hexafluoroacetone with formic acid.

8. The process of producing 2H-hexafluoro-2-propanol according to claim 1 which comprises reacting hexafluoroacetone with methanol.

9. The process of producing ZH-hexafiuoro-Z-propanol according to claim 1 which comprises reacting hexafluoroacetone with formaldehyde.

10. The process of producing ZH-hexafluoro-Z-propan01 according to claim 1 which comprises reacting hexafiuoroacetone with isopropyl alcohol.

11. 1H-hexafiuorocyclobutanol.

References Cited UNITED STATES PATENTS 4/ 1962 Andreades et al. 2/ 1964 Lindsey et al. 4/ 1964 Castle. 

1. THE PROCESS OF PRODUCING A SECONDARY FLUOROALCOHOL WHICH COMPRISES REACTING, AT A TEMPERATURE BETWEEN 100 AND 400*C. AND AT AT LEAST AUTOGENOUS PRESSURE, A POLYFLUOROKETONE OF THE FORMULA 